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We have characterized two RNA-binding proteins, of apparent molecular masses of approximately 40 and 35 kDa, which possess a single N-terminal RNA-recognition motif (RRM) followed by a C-terminal domain rich in serine-arginine dipeptides. Their primary structures resemble the single-RRM serine-arginine (SR) protein, SC35; however their functional effects are quite distinctive. The 40-kDa protein cannot complement SR protein-deficient HeLa cell S100 extract and showed a dominant negative effect in vitro against the authentic SR proteins, SF2/ASF and SC35. Interestingly, the 40- and 35-kDa proteins antagonize SR proteins and activate the most distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo, an activity that is similar to that characterized previously for the heterogeneous nuclear ribonucleoprotein particles A/B group of proteins. A series of recombinant chimeric proteins consisting of domains from these proteins and SC35 in various combinations showed that the RRM, but not the C-terminal domain rich in serine-arginine dipeptides, has a dominant role in this activity. Because of the similarity to SR proteins we have named these proteins SRrp40 and SRrp35, respectively, for SR-repressor proteins of approximately 40 and approximately 35 kDa. Both factors show tissue- and cell type-specific patterns of expression. We propose that these two proteins are SR protein-like alternative splicing regulators that antagonize authentic SR proteins in the modulation of alternative 5' splice site choice.

Original publication




Journal article


J Biol Chem

Publication Date





48908 - 48914


3T3 Cells, Active Transport, Cell Nucleus, Alternative Splicing, Amino Acid Sequence, Animals, Cell Cycle Proteins, Cell Nucleus, Cloning, Molecular, Genes, Reporter, HeLa Cells, Humans, Immunohistochemistry, Mice, Molecular Sequence Data, Molecular Weight, Neoplasm Proteins, RNA-Binding Proteins, Recombinant Fusion Proteins, Repressor Proteins, Sequence Alignment, Serine-Arginine Splicing Factors, Tissue Distribution